Tissue culture experiments employing human arterial cells are proposed to study accelerated atherosclerosis which limits the survival of renal failure patients treated both by dialysis and transplantation. Since proliferation of the arterial smooth muscle cell (SMC) is a sine qua non for atherogenesis, specific studies are proposed to identify factors in these patients which play a role in the control of cell proliferation. This type of experimental approach examines for the first time the interaction of circulating factors believed to be important in atherogenesis with the specific cell which causes the lesion. Current experiments in the principal investigator's laboratory which indicate that circulating substances present in these renal patients which significantly stimulate SMC growth, will be extended: blood will be separated into serum and plasma, and further fractionated by ion exchange and molecular sieve chromatography to characterize the mitogenic substance(s). Lipoproteins in these patients shown by the principal investigator to have abnormal neutral lipid composition will be isolated by ultracentrifugal techniques and their mitogenic properties quantitated. The influences of serum/plasma from these renal patients on the interaction between SMC and plasma lipoproteins will be further examined in studies of the binding, uptake and degradation of 125I-LDL. In related studies the effects of HDL from controls and renal patients on these parameters of LDL transport will be compared. Since SMC have been shown to form most connective tissue in the normal arterial wall, and one of these substances--proteoglycans--increases prior to lipid deposition in experimental arteriosclerosis, the effects on proteoglycan synthesis and secretion of factors found to be mitogenic on SMC also will be studied. The vascular injury hypothesis of atherosclerosis in renal failure will be tested with human endothelial cells (EC) in experiments in which the effects of factors present in the circulation including the medications used by transplant patients for immunosuppression will be assessed.